Similar Conduction Velocities Research Articles

Noninvasive stratification of ventricular substrate by electrocardiographic imaging

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Abnormalities of cardiac activation and conduction velocity (CV) are known pro-arrhythmogenic factors. Electrocardiographic imaging (ECGI) is presented as a non-invasive tool for arrhythmogenic substrate analysis. However, electrocardiographic features such propagation activation patterns, and CV are unknown in healthy subjects. In this study, ECGI technology has been evaluated for ventricular tissue stratification in patients with and without structural heart disease. Methods Nineteen patients were included in the study. The healthy ventricles group (Panel A) included 10 patients (8 males, 57 ± 6 years, NYHA = I and LVEF 61 ± 5 %) with normal baseline QRS and normal values of ventricular morphology, function and perfusion assessed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). The structural heart disease group (Panel B) included 9 patients (9 males, 66±6 years, NYHA 2±1 and LVEF 26±5%) with ischemic cardiomyopathy (ICM) confirmed by LGE-CMR and indication for ablation due to ventricular tachycardia. For each patient, fibrotic areas were identified by ventricular segmentation of the LGE-CMR and ventricles were regionalized in 16 regions. Epicardial electrograms were noninvasively reconstructed by ECGI, late activation time (LAT) and CV maps were calculated to study electrocardiographic features. Results – Ventricles with fibrosis secondary to ICM revealed heterogenous activation patters and higher activation time distribution compared to healthy ventricles (120 ms vs 80 ms; p<0.01). Density distribution of CV was evaluated in the 0-200 cm/s interval, patients with healthy ventricular tissue showed homogenous CV distribution whereas ICM patients presented higher concentration in the slow CV region with a maximum peak around 75 cm/s. Moreover, CV values were significantly lower in fibrotic myocardium present in patients with structural heart disease compared to healthy myocardium (77 ± 40 cm/s vs 114 ± 46 cm/s; p<0.01), Panel C anterior view. Non-fibrotic regions in the ischemic ventricle group, Panel C inferior view, presented similar CV distributions to healthy ventricular tissue (114 ± 46 cm/s vs 120 ± 48 cm/s; p = 0.14). Conclusions ECGI can noninvasively identify fibrotic tissue by analysing ventricular activation and CV patterns. ECGI could be a potential early tool to identify patients at risk of sudden cardiac death.

PO-02-231 NON-INVASIVE STRATIFICATION OF VENTRICULAR SUBSTRATE BY ELECTROCARDIOGRAPHIC IMAGING

Abnormalities of cardiac activation and conduction velocity (CV) are known pro-arrhythmogenic factors. Electrocardiographic imaging (ECGI) is presented as a non-invasive tool for arrhythmogenic substrate analysis. However, electrocardiographic features such as propagation activation patterns, and CV are unknown in healthy and ischemic subjects. To evaluate the ECGI technology for ventricular tissue stratification in patients with and without structural heart disease. Nineteen patients were included in the study. The healthy ventricles group (Figure - Panel A) included 10 patients (8 males, 57 ± 6 years, NYHA = I and LVEF 61 ± 5 %) with normal baseline QRS and normal values of ventricular morphology, function, and perfusion assessed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). The structural heart disease group (Figure - Panel B) included 9 patients (9 males, 66±6 years, NYHA 2±1 and LVEF 26±5%) with ischemic cardiomyopathy (ICM) confirmed by LGE-CMR and indication for catheter ablation due to ventricular tachycardia. For each patient, fibrotic areas were identified by ventricular segmentation of the LGE-CMR, and ventricles were regionalized into 16 regions. Epicardial electrograms were noninvasively reconstructed by ECGI, local activation time (LAT) maps, and CV maps were calculated to study electrocardiographic features. Ventricles with fibrosis secondary to ICM revealed heterogeneous activation patterns and higher activation time distribution compared to healthy ventricles (120 ms vs 80 ms; p<0.01). The density distribution of CV was evaluated in the 0-200 cm/s interval, patients with healthy ventricular tissue showed homogenous CV distribution whereas ICM patients presented higher concentration in the slow CV region with a maximum peak around 75 cm/s. Moreover, CV values were significantly lower in fibrotic myocardium present in patients with structural heart disease compared to healthy myocardium (77 ± 40 cm/s vs 114 ± 46 cm/s; p<0.01), Figure-Panel C anterior view. Non-fibrotic regions in the ischemic ventricle group, Figure - Panel C inferior view, presented similar CV distributions to healthy ventricular tissue (114 ± 46 cm/s vs 120 ± 48 cm/s; p = 0.14). ECGI can noninvasively identify fibrotic tissue by analyzing ventricular activation and CV patterns. ECGI could be a potential early tool to identify patients at risk of sudden cardiac death.

Role of AMPK pathway inactivation in high fat diet related cardiac electrophysiological remodeling.

Although impaired AMPK signaling is a hallmark of metabolic diseases (MetD), which heighten arrhythmia risk, whether and how loss of AMPK activity per se promotes adverse electrophysiological (EP) remodeling independently of confounding factors in MetD remains unknown. We investigated the EP substrate of wildtype (WT) mice on high-fat diet (HFD) relative to those on normal diet (ND) and to mice expressing the muscle-specific AMPK kinase dead isoform (AMPK-KD). After 8-weeks of HFD, mice underwent hemodynamic analysis by echocardiography and ex vivo optical action potential (AP) mapping. While HFD-fed mice did not exhibit structural or hemodynamic changes by 8-weeks, they were more prone to pacing-induced VT than their ND counterparts (57% HFD vs 11% ND). Investigation of the EP substrate revealed a marked decrease in conduction velocity (CV) in HFD vs ND-fed mice (54.9±6.7 cm/s vs 71.6±10.2 cm/s, p<0.05) with no change in AP duration (APD). Importantly, we found similar CV slowing in AMPK-KD on ND as WT on HFD. Challenging AMPK-KD mice with HFD did not reduce CV further (45.4±10.6 cm/s HFD vs 49.0±11.1 cm/s ND). In contrast, APD was decreased exclusively in AMPK-KD mice on HFD, reflecting the importance of both factors (AMPK depletion and HFD) in the modulation of myocardial repolarization. Functionally, the subset of hearts that were prone to HFD-related VT exhibited decreased CV compared to those that were protected against VT. We examined the molecular correlates of myocardial conduction, and found a paradoxical increase in Nav1.5, total and Ser368-phosphorylated Cx43 in AMPK-KD, discounting overall protein expression as a factor in CV slowing. In conclusion, impaired AMPK signaling accounts for early CV defects in HFD prior to onset of structural or mechanical remodeling. Our findings highlight AMPK as a potentially powerful anti-arrhythmic target at early stages of MetD.

BI-ATRIAL MAPPING AND ELEVATED HEART RATES IDENTIFY ABNORMAL ATRIAL SUBSTRATE IN ATRIAL FIBRILLATION PATIENTS WITHOUT LOW-VOLTAGE AREAS IN THE LEFT ATRIUM

BI-ATRIAL MAPPING AND ELEVATED HEART RATES IDENTIFY ABNORMAL ATRIAL SUBSTRATE IN ATRIAL FIBRILLATION PATIENTS WITHOUT LOW-VOLTAGE AREAS IN THE LEFT ATRIUM

Cardiac reparative therapy with adipose graft transposition procedure reduces slow conduction areas in a chronic myocardial infarction swine model

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Insituto de Salud Carlos III BACKGROUND Cardiac regenerative therapy is a promising treatment for patients with ischemic heart disease, but there are some concerns on the potential increased risk of arrhythmic events following specific cell therapies. Adipose graft transposition procedure (AGTP) is a cardiac reparative therapy consisting in transposing a vascularized adipose flap from the autologous pericardium and placing it over the epicardial scar area and has demonstrated to reduce infarct size and improve the left ventricular ejection fraction in preclinical and human studies. Specific electrophysiological properties of the scar, (i.e. slow conduction velocity (CV)) have been identified as key features of ventricular tachycardia (VT) isthmuses. PURPOSE To assess the effect of the AGTP on VT inducibility and the electrophysiological properties of the post-MI scar with ultra-high density (UHD) mapping. METHODS A left circumflex artery (first marginal branch) MI was induced in 10 Landrace X Large White pigs by delivering 1-3 coils. Two weeks post-MI, all subjects underwent baseline left ventricular endocardial UHD mapping during right ventricular pacing with 64-electrode basket mapping catheter, as well as electrophysiological study (EPS) to test for VT inducibility. Following the mapping, subjects were allocated 1:1 to AGTP or sham group. UHD mapping and EPS were repeated 30 days post-treatment (6 weeks after MI). Voltage and activation maps were analyzed off-line with self-customized Paraview-based software. Voltage cut-offs of 1.5 and 0.5mV (bipolar) defined normal tissue, border zone (BZ) and dense scar, respectively, and 6.7mV for unipolar. Conduction velocity (CV) was determined for every pair of contiguous points and areas of similar CV were quantified for every 0.2m/s steps (for up to 4 m/s). RESULTS There were no differences between groups with regard of dense scar, BZ an low unipolar voltage areas. The AGTP group had a significant reduction of the size of slow CV (&amp;lt;0.2 m/s) areas, compared to the sham group in whom it increased (-4.1 ± 1.7 vs. +2.4 ± 1.6 mm2, p = 0.028)(Figure). There were no differences in the size of other ranges of CV. EPS did not induce VT in any subject at baseline, and only in 1 of the sham group at the follow-up EPS. CONCLUSIONS Cardiac reparative therapy with AGTP of post-MI scar reduced the size of slow conduction areas and could provide a protective effect against arrhythmic events in ischemic heart disease. Abstract Figure.

Investigating changes in global conduction velocity estimates from biceps brachii muscles of stroke survivors

It has been inferred that stroke-induced alterations of the lower motor neurons and their muscle fibres may contribute to muscle weakness and thus to motor impairment. Although previous accounts have investigated the mechanisms underpinning muscle weakness from muscle fiber conduction velocity estimates, reports about how the global conduction velocity (CV) differ between healthy and paretic muscles post-stroke are uncommon. Thus, in this study we examined side-differences in global CV estimates from biceps brachii muscles of stroke survivors, and their relation with differences between muscles’ functions. Seven chronic post-stroke patients participated in this study. Surface electromyograms were sampled with a grid of 32 electrodes (8 × 4; 10 mm inter-electrode distance) from biceps brachii. Stimulation electrodes were placed in bipolar configuration as proximally as possible over the muscle. CV values were estimated from differential M waves elicited by supramaximal current pulses. Impairment of biceps brachii functions was assessed with the Fugl-Meyer Assessment scale. Spearman's rank-order correlation was applied to verify the relationship of the healthy/paretic ratio values for CV and Fugl-Meyer values. There was a significant negative correlation (Rho = −0.96; P = 0.003; n = 7: Fig. 1 ) between side-differences in CV values and the functional scores. Marked differences in CV values estimated for the healthy and paretic limbs were associated with highly impaired, biceps brachii function. Conversely, patients with either preserved or recovered motor function exhibited similar CV values for both limbs. Whether these side-differences in CV may be explained by structural adaptations remains an open issue. Current results reveal however the CV values may constitute a relevant index to assess the degree of motor function in biceps brachii motor units.

P2-2-03. Severity classification of diabetic polyneuropathy in type 1diabetes mellitus

Evaluation of the severity of diabetic polyneuropathy (DPN) is recommended according to Baba’s criteria (Baba M, Japanese Journal of Clinical Neurophysiology 2013). It is mainly studied in type 2 diabetes mellitus (DM). We examined whether these are also compatible with type 1 DM. Thirty-eight patients with type 1 DM were enrolled (21 female, mean age 59.6 ± 13.8 yo, mean clinical course 16.2 ± 9.4 years, mean HbA1c 7.8 ± 1.3%) and were compared with forty-two patients with type 2 DM. Nerve conduction studies of tibial and sural nerves were examined. All the patients with type 2 DM were applicable to Baba’s criteria. However, seven type 1 patients (18%) were not applicable. They disclosed abnormally small amplitude of sural nerve action potential, while the conduction velocity and minimum F wave latency of the tibial nerve were normal. Compound muscle action potentials of this nerve were normal as well. Among these seven patients, six showed the decreased Achilles tendon reflex, while it was preserved in the type 1 patients who showed similar conduction velocities and minimum F latency of the tibial nerve. These results suggest the different mechanism contribute to the pathophysiology between type 1 and type 2 DM, leading to sensory dominant axonal polyneuropathy without motor involvement in about 20% of patients with type1 DM.

Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis.

BackgroundIncreased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated.MethodsHigh-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.ResultsTC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (−10.2±1.5 versus −5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (−22.3±1.1 versus −9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L.ConclusionOur findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.

Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials.

Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs.

Alternans by non-monotonic conduction velocity restitution, bistability and memory

Conduction velocity (CV) restitution is a key property that characterizes any medium supporting traveling waves. It reflects not only the dynamics of the individual constituents but also the coupling mechanism that mediates their interaction. Recent studies have suggested that cardiac tissues, which have a non-monotonic CV-restitution property, can support alternans, a period-2 oscillatory response of periodically paced cardiac tissue. This study finds that single-hump, non-monotonic, CV-restitution curves are a common feature of in vitro cultures of rat cardiac cells. We also find that the Fenton–Karma model, one of the well-established mathematical models of cardiac tissue, supports a very similar non-monotonic CV restitution in a physiologically relevant parameter regime. Surprisingly, the mathematical model as well as the cell cultures support bistability and show cardiac memory that tends to work against the generation of an alternans. Bistability was realized by adopting two different stimulation protocols, ‘S1S2’, which produces a period-1 wave train, and ‘alternans-pacing’, which favors a concordant alternans. Thus, we conclude that the single-hump non-monotonicity in the CV-restitution curve is not sufficient to guarantee a cardiac alternans, since cardiac memory interferes and the way the system is paced matters.

The Relationship Between Conduction Velocity and Atrial Arrhythmogenicity under Conditions of Altered Ca2+ Homeostasis in RyR2-P2328S Murine Hearts

Atrial fibrillation (AF) is a significant contributor to mortality and health care expenditure; it is associated with abnormal sarcoplasmic reticulum (SR) Ca2+ release through cardiac ryanodine receptors. The initiation of AF requires an ectopic action potential (AP) triggered within a substrate of atria conducive to the formation of re-entry circuits. The present experiments explored whether increased diastolic SR Ca2+ release might contribute to atrial arrhythmogenicity in homozygotic gain-of-function RyR2-P2328S mice (RyR2s/s).Electrocardiographs and intracellular APs were recorded from Langendorff-perfused hearts at regular 8 Hz (S1) stimulation. RyR2s/s hearts showed depolarised resting membrane potentials that were associated with an increased incidence of ectopic APs and sustained tachyarrhythmias. During regular stimulation, the RyR2s/s showed reduced epicardial conduction velocities (CV), measured using a 64-electrode array, that corresponded with reduced S1 AP upstroke velocities ((dV/dt)max).When ectopic (S2) APs were imposed during S1 stimulation at progressively shorter S1S2 intervals, the inter-atrial CV and dV/dt(max) of the S2 APs decreased with each successive interval. Moderate reductions in S1S2 interval provoked sustained tachyarrhythmias in RyR2s/s hearts, whereas significantly shorter S1S2 intervals were required to provoke arrhythmias in WT hearts. Interestingly, the mean S1S2 interval required to provoke an arrhythmia in each variant resulted in similar inter-atrial CVs and dV/dt(max).These findings suggest that triggered activity is likely to lead to a sustained tachyarrhythmia in murine atria only when the CV of an ectopic AP is slow (<∼1.1 m/s). We have shown this is more likely to occur in RyR2s/s atria where increased diastolic SR Ca2+ release is associated with both increased ectopic APs and an intrinsically slow CV. We therefore suggest that abnormal Ca2+ homeostasis contributes to both the trigger and the re-entry substrate in sustained atrial tachyarrhythmias.

The Regularity of Sustained Firing Reveals Two Populations of Slowly Adapting Touch Receptors in Mouse Hairy Skin

Touch is initiated by diverse somatosensory afferents that innervate the skin. The ability to manipulate and classify receptor subtypes is prerequisite for elucidating sensory mechanisms. Merkel cell-neurite complexes, which distinguish shapes and textures, are experimentally tractable mammalian touch receptors that mediate slowly adapting type I (SAI) responses. The assessment of SAI function in mutant mice has been hindered because previous studies did not distinguish SAI responses from slowly adapting type II (SAII) responses, which are thought to arise from different end organs, such as Ruffini endings. Thus we sought methods to discriminate these afferent types. We developed an epidermis-up ex vivo skin-nerve chamber to record action potentials from afferents while imaging Merkel cells in intact receptive fields. Using model-based cluster analysis, we found that two types of slowly adapting receptors were readily distinguished based on the regularity of touch-evoked firing patterns. We identified these clusters as SAI (coefficient of variation = 0.78 +/- 0.09) and SAII responses (0.21 +/- 0.09). The identity of SAI afferents was confirmed by recording from transgenic mice with green fluorescent protein-expressing Merkel cells. SAI receptive fields always contained fluorescent Merkel cells (n = 10), whereas SAII receptive fields lacked these cells (n = 5). Consistent with reports from other vertebrates, mouse SAI and SAII responses arise from afferents exhibiting similar conduction velocities, receptive field sizes, mechanical thresholds, and firing rates. These results demonstrate that mice, like other vertebrates, have two classes of slowly adapting light-touch receptors, identify a simple method to distinguish these populations, and extend the utility of skin-nerve recordings for genetic dissection of touch receptor mechanisms.

The impact of extended electrodiagnostic studies in ulnar neuropathy at the elbow.

BackgroundThis study aimed to explore the value of extended motor nerve conduction studies in patients with ulnar nerve entrapment at the elbow (UNE) in order to find the most sensitive and least time-consuming method. We wanted to evaluate the utility of examining both the sensory branch from the fifth finger and the dorsal branch of the ulnar nerve. Further we intended to study the clinical symptoms and findings, and a possible correlation between the neurophysiological findings and pain.MethodsThe study was prospective, and 127 UNE patients who were selected consecutively from the list of patients, had a clinical and electrodiagnostic examination. Data from the most symptomatic arm were analysed and compared to the department's reference limits. Student's t - test, chi-square tests and multiple regression models were used. Two-side p-values < 0.05 were considered as significant.ResultsUlnar paresthesias (96%) were more common than pain (60%). Reduced ulnar sensitivity (86%) and muscle strength (48%) were the most common clinical findings. Adding a third stimulation site in the elbow mid-sulcus for motor conduction velocity (MCV) to abductor digiti minimi (ADM) increased the electrodiagnostic sensitivity from 80% to 96%. Additional recording of ulnar MCV to the first dorsal interosseus muscle (FDI) increased the sensitivity from 96% to 98%. The ulnar fifth finger and dorsal branch sensory studies were abnormal in 39% and 30% of patients, respectively. Abnormal electromyography in FDI was found in 49% of the patients. Patients with and without pain had generally similar conduction velocity parameter means.ConclusionWe recommend three stimulation sites at the elbow for MCV to ADM. Recording from FDI is not routinely indicated. Sensory studies and electromyography do not contribute much to the sensitivity of the electrodiagnostic evaluation, but they are useful to document axonal degeneration. Most conduction parameters are unrelated to the presence of pain.

Selective Role for TRPV4 Ion Channels in Visceral Sensory Pathways

Although there are many candidates as molecular mechanotransducers, so far there has been no evidence for molecular specialization of visceral afferents. Here, we show that colonic afferents express a specific molecular transducer that underlies their specialized mechanosensory function: the transient receptor potential channel, vanilloid 4 (TRPV4). We found TRPV4 mRNA is highly enriched in colonic sensory neurons compared with other visceral and somatic sensory neurons. TRPV4 protein was found in colonic nerve fibers from patients with inflammatory bowel disease, and it colocalized in a subset of fibers with the sensory neuropeptide CGRP in mice. We characterized the responses of 8 subtypes of vagal, splanchnic, and pelvic mechanoreceptors. Mechanosensory responses of colonic serosal and mesenteric afferents were enhanced by a TRPV4 agonist and dramatically reduced by targeted deletion of TRPV4 or by a TRP antagonist. Other subtypes of vagal and pelvic afferents, by contrast, were unaffected by these interventions. The behavioral responses to noxious colonic distention were also substantially reduced in mice lacking TRPV4. These data indicate that TRPV4 contributes to mechanically evoked visceral pain, with relevance to human disease. In view of its distribution in favor of specific populations of visceral afferents, we propose that TRPV4 may present a selective novel target for the reduction of visceral pain, which is an important opportunity in the absence of current treatments.

Abstract 1344: Biphasic Effect of Electrotonic Fibroblast-Myocyte Coupling on 2D Wave Conduction Velocity and Reentry

Fibroblast proliferation is common to various cardiac diseases. Differentiation of fibroblasts into myofibroblasts may result in myocyte-fibroblast electrical coupling via gap junctions. We hypothesized that fibroblast proliferation and varying heterocellular coupling significantly alter 2-dimensional cardiac wave propagation and reentry dynamics. Methods : Monolayers of co-cultured fibroblasts and myocytes from neonatal rat ventricles were optically mapped. The junctional coupling was reduced using Cx43 RNA silencer in the fibroblasts. Simulations were used to quantify the effects of heterocellular coupling variation. Conduction velocity (CV) was measured when pacing at 2 Hz. Results : Experiments and simulations show linear CV and reentry frequency reduction with increased number of wavebreaks as fibroblast/myocyte mixed area ratio increases. However, simulations show that the effect of fibroblast-myocyte coupling on CV and reentry frequency is biphasic: as coupling increases reentry frequency and CV initially decrease and then increase. Panel A shows that for a 1/4 fibroblasts/myocytes mixture the minimum CV is at ~10% of the myocytes coupling. In both experiments and simulations, low heterocellular coupling can result in similar CV and frequency of rotation (p&lt;0.05), but more fragmented wavefronts as compared with high coupling (panel B). Conclusion: Fibroblasts may have a dual role as current “sinks” and “transmitters”, depending on the level of heterocellular coupling. This study provides novel insight into the mechanisms whereby electrical interactions between myocytes and fibroblasts modify wave propagation and the propensity to arrhythmias.

Rate‐Dependent Block in the Sinus Venosa of the Swine Heart during Transverse Right Atrial Activation: Correlation Between Electrophysiologic and Anatomic Findings

Rate-dependent block in the sinus venosa. Whether the crista terminalis or the sinus venosa result in rate-dependent block during transverse activation of the right atrial activation remains unknown. In the present study, right atrial activation at different cycle lengths was studied in the swine heart using high-resolution noncontact mapping (Endocardial Solutions). The location of the block was tagged and correlated with postmortem anatomical findings. Eight pigs were studied using noncontact mapping to obtain right atrial geometry and detailed sequence of activation using noncontact endocardial mapping. During sinus rhythm, activation proceeded uninterrupted craniocaudally along the sinus venosa and crista terminalis with similar conduction velocities (1.08+/-0.17 and 1.17+/-0.14 m/sec, respectively). Proximal coronary sinus stimulation was used to create transverse activation of the posterior right atrial wall. A rate-dependent decrease in conduction velocity occurred in the sinus venosa region (0.93+/-0.21, 0.82+/-0.14, and 0.52+/-0.09 m/sec at 500, 400, and 300 ms, respectively; P<0.05). The line of block verified by isopotential mapping and double potentials was obtained at cycle lengths of 240+/-30 ms. This line of the block was tagged with radiofrequency current lesions. Postmortem, all lesions were located in the sinus venosa region, 9.8+/-4.1 mm from the posteromedial edge of the crista terminalis. This region showed abrupt changes in muscle fiber thickness and orientation as well as in collagen content. The sinus venosa and not the crista terminalis results in a rate-dependent line of block during transverse right atrial activation. The morphologic characteristics of the sinus venosa appear to facilitate block in this region.

Nerve function in experimental diabetes in rats: effects of electrical stimulation.

The effects of unilateral electrical stimulation of the peroneal sciatic nerve branch were studied in streptozocin-diabetic rats of 12-wk duration. Stimulation was carried out over 7 days (10 Hz, 8 h/day) with chronically implanted electrodes. Compared with controls, there was a 25% conduction velocity (CV) deficit for the peroneal nerve supplying tibialis anterior muscle in the unstimulated leg, which was corrected by stimulation. For tibial fibers supplying soleus muscle, a similar diabetic CV deficit (20%) was normalized by stimulation, although soleus axons were not directly activated. In saphenous nerve, which has a functionally separate vascular supply, peroneal stimulation was ineffective. In anesthetized diabetic rats, stimulation caused an 18% reduction in tibialis anterior CV after 4 h. However, serial measurements showed progressive normalization of CV over 4 days of stimulation. On termination, CV returned to diabetic levels over 36-60 h. Sciatic nerve showed a 70% increase in resistance to hypoxic conduction failure with diabetes, which was halved by chronic stimulation. Acute experiments demonstrated that peroneal stimulation increased sciatic vascular conductance by 60%. We conclude that stimulation causes activity-related improvements in diabetic nerve blood flow and metabolism.

Influence of synaptic identity on single-Ia-afferent connectivity and EPSP amplitude in the adult cat: homonymous versus heteronymous connections.

1. This study makes use of the pattern of synaptic connections between motoneurons and Ia afferents of triceps surae muscles in the cat to test the relative importance of synaptic identity, neuronal size, and neuronal topography as determinants of Ia-afferent connectivity and excitatory postsynaptic potential (EPSP) amplitude. 2. The synaptic actions of single-Ia medial gastrocnemius (MG) afferents were measured by intracellular recording in MG and lateral gastrocnemius (LG) motoneurons. The spike-triggered averaging technique was used to measure EPSPs generated by homonymous or heteronymous Ia afferents and motoneurons, i.e., neurons supplying the same or different muscles, respectively. In agreement with earlier studies, the pooled sample showed that the number of functional connections and the size of EPSPs were both significantly greater for homonymous than for heteronymous neurons. 3. Afferent conduction velocity, motoneuron conduction velocity, rheobase current, and position of the motoneuron relative to the spinal cord afferent entry were all correlated with EPSP amplitude, but the amplitude difference between homonymous and heteronymous connections remained significant after the statistical removal analysis of covariance (ANCOVA) of the contribution of these variables. Stepwise multiple-regression analysis showed that synaptic identity explained the greatest fraction of the variance in EPSP amplitude (9%), with significant but smaller fractions accounted for by rheobase current or motoneuron conduction velocity. 4. In a separate experiment, the monosynaptic affects from both homonymous and heteronymous single-Ia afferents were examined in each of 88 MG or LG motoneurons. The single-Ia afferents used in this portion of the study were sampled from both MG and LG muscles and selected for similar conduction velocities and spinal cord entry points.(ABSTRACT TRUNCATED AT 250 WORDS)

Nerve conduction in the hands of vibration exposed workers

Symptoms of peripheral neuropathy in the hands are common among workers using vibrating tools. The mechanism for this and its relation to carpal tunnel syndrome (CTS) was studied in workers exposed to vibration at their workplace (17), along with a control group of healthy construction workers with heavy manual work but without vibration exposure (10). Patients with uni- or bilateral CTS (11) and a group of healthy volunteers without manual work (9) were included for comparison. Median nerve conduction velocities were measured both over the carpal tunnel and in a more distal segment. Vibration exposed workers had similar conduction velocities to unexposed construction workers. The subgroup of vibration exposed patients with symptoms from the hands had normal conduction in the ulnar nerve but demonstrated a decrease in median nerve conduction comparable (but less pronounced) with the CTS group. On a group basis these results indicated that the median nerve is most vulnerable for hand-arm vibrations. However, the conduction defects were not pronounced enough to diagnose CTS in most individual cases.

Changes in axonal impulse conduction correlate with sensory modality in primary afferent fibers in the rat

Conduction velocity was measured in vivo in single cutaneous afferent fibers of rat sciatic nerve that were characterized by natural stimulation. During sustained electrical stimulation, impulses slowed less and propagated more reliably in cold fibers (both Aδ and C) than in nociceptive fibers of similar conduction velocity. Velocity in cold fibers tended to stabilize after an initial decrease rather than decrease throughout the stimulation as for nociceptive fibers. The slowing correlated with axon modality and hence with natural firing pattern, raising the possibility that impulse activity can determine conduction properties of axons.